The specific aims of the proposed research are to investigate the role of voltagegated sodium channels in back-propagation of action potentials in the dendrites of neocortical cells. Specifically, we will determine whether modulation of slow inactivation in sodium channels is responsible for an increase in sodium channel availability that underlies back propagation of action potentials into dendrites. The hypotheses we will test are that (1) an increase in sodium channel availability is the basis for dendritic electrogenesis in response to high frequency discharges, and (2) modulation of sodium channels by cell signaling pathways is responsible for an decrease in steady-state probability of slow inactivation which leads to increased channel availability. The health-relatedness of the proposed research is that back propagation is an important regulator of synaptic efficacy. Understanding the biophysical basis for back propagation will help researchers understand the physiological mechanisms of learning and memory.